The field of the invention relates to the use of lipid particles for delivering biological molecules to target cells. In particular, the field of the invention relates to engineered exosomes that contain and are used to target and deliver cargo RNA molecules to a target cell.
Exosomes are nanometer-scale lipid vesicles that are produced by many cell types and transfer proteins, nucleic acids, and other molecules between cells in the human body, as well as those of other animals. RNA-loaded exosomes have a wide variety of potential therapeutic uses and are already being investigated as delivery vehicles for gene therapy, vaccines, and reprogramming factors in the generation of pluripotent stem cells. However, the therapeutic utility of exosomes is hampered by a general lack of control over which molecules are loaded from the exosome-producer cell into the exosomes. Of particular relevance, efficiently loading of certain RNA species into exosomes is not possible using current technologies. The Targeted And Modular Exosome Loading (TAMEL) system described here is a technology for loading specific target RNAs into exosomes, in a manner that is independent of natural mechanisms for exosome loading. Thus, this technology enables control over which RNA species are most abundant in exosomes and may enable loading of various therapeutically-relevant RNA species.